DESCRIPTION: Applicant's Abstract The proposed 5 year project will quantify adherence with combination antiretroviral therapy in a well established longitudinal cohort of HIV-infected drug users in the Bronx, New York City, and will determine the impact of differing levels of adherence on changes in HIV viral load and development of antiviral resistance. Combined antiretroviral therapy can profoundly inhibit viral replication and markedly delay disease progression, but achieving this potential in clinical practice requires adherence to complex medical regimens. Nonadherence may result not only in reduced treatment efficacy, but also in the selection of drug-resistant HIV strains. There is active debate about the circumstances under which combination antirotroviral therapy should be available to drug users because of concerns about poor adherence to disseminated multi-drug resistant HIV, but the true extent of adherence with combination antiretroviral therapy among drug users is not known. The specific aims of the proposed research include: (1) determining tho extent of adherence with combination antiretroviral therapy among drug users; (2) examining the impact of differing patterns of adherence on HIV disease outcomes, including viral load and antiretroviral drug resistance; (3) investigating prospectively HIV- and medication-specific beliefs and other psychosocial predictors of adherence; and (4) identifying sociodemographic, cultural and clinical characteristics that influence adherence. The study design includes the use of state-of-the-art electronic medication monitors and patient self report to assess medication-taking adherence in 175 known HIV-seropositive drug users recruited from 10-year old HERO cohort at Montefiore Hospital. At monthly research visits, adherence data will be downloaded from the electronic device and blood will be drawn for HIV viral load quantification and drug resistance studies. Phenotypic and genotypic drug resistance assays will be performed on all subjects who have clinically meaningful increases in HIV viral load. Quantification of viral load and generation of HIV isolates will be performed by Dr. H. Farzadegan (Johns Hopkins University), and drug resistance assays by Dr. V. Prasad (Albert Einstein College of Medicine). This prospective study design will allow characterization of the exact relationship between adherence patterns, viral load, and development of drug resistance.